Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME). Chronic treatment with L-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 +/- 16 mmHg) as compared to controls (155 +/- 4 mmHg). Animals receiving simultaneously L-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56 +/- 0.73 ml.kg-1.min-1) and renal plasma flow (RPF: 6.93 +/- 1.70 ml.kg-1.min-1) as compared to control (GFR: 7.29 +/- 0.69, RPF: 21.36 +/- 2.33 ml.kg-1.min-1). Addition of ramipril prevented L-NAME-induced reduction in GFR and renal plasma flow. L-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with L-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. 753 99

Using a porphyritic microsensor, we measured the cortical NO concentration within ischemic tissue during 2 h of middle cerebral artery (MCA) occlusion and 1 h of reperfusion in the rat (n = 36). Local cerebral blood flow was simultaneously measured by laser Doppler flowmetry to verify MCA occlusion and reperfusion. Baseline concentration of NO was < 10(-8) M. The maximum concentrations of NO during MCA occlusion and reperfusion were, respectively, 1.47 +/- 0.45 microM and 0.54 +/- 0.24 microM. Administration of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, prior to ischemia, significantly (p < 0.05) reduced NO release to 0.04 +/- 0.02 microM during MCA occlusion and completely inhibited NO release during 1 h of reperfusion. Administration of L-arginine 30 min after administration of L-NAME restored NO release (3.45 +/- 1.14 microM) during MCA occlusion; however, administration of L-arginine did not overcome the effect of L-NAME on mean arterial blood pressure. Our data indicate that NO is released in the brain after the onset of ischemia and NO levels can be modulated by administration of NO substrate and NO antagonists.
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PMID:Nitric oxide changes in the rat brain after transient middle cerebral artery occlusion. 753 15

Nitric oxide, a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia as it may facilitate collateral blood flow to the ischemic territory. Accordingly, the effect of inhibition of nitric oxide synthesis on cerebral ischemic damage may vary depending on the timing of the inhibition relative to the induction of ischemia. We therefore studied the time course of the effect of nitric oxide synthesis inhibition on focal cerebral ischemic damage. The middle cerebral artery was permanently occluded in spontaneously hypertensive rats and the nitric oxide synthase (NOS) inhibitor nitro-L-arginine methyl ester (L-NAME) was administered systemically (3 mg/kg) < 5 min or 2, 3, or 6 h later. Arterial pressure, rectal temperature, plasma glucose, and hematocrit were monitored. Infarct volume was determined on thionin-stained sections 24 h after induction of ischemia. NOS activity was determined in cerebellum from the conversion of L-[3H]arginine to L-[3H]citrulline. Administration of L-NAME < 5 min after arterial occlusion increased the infarct volume by 23 +/- 14% (mean +/- SD; p < 0.05, analysis of variance), while administration of L-NAME at 2 or 6 h did not affect the size of the infarct (p > 0.05). L-NAME administration 3 h after induction of ischemia reduced neocortical infarct size by 14 +/- 11% (p < 0.05). L-NAME decreased cerebellar NOS activity comparably in all groups (range 16-25%). We conclude that the effects of inhibition of nitric oxide synthesis on focal cerebral ischemic damage are time dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time dependence of effect of nitric oxide synthase inhibition on cerebral ischemic damage. 754 Jun 21

Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a significantly greater decline in RBF to intravenous L-NAME in NE- than sham-ARF rats (-65 +/- 8 vs. -37 +/- 5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham- and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity is in response to ischemia-induced renal vasoconstrictor activity. Attenuated response to endothelium-dependent vasodilators cannot be interpreted only as evidence for decreased NOS activity.
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PMID:Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats. 754 87

We tested the hypothesis that inhibition of nitric oxide synthase (NOS) activity in brain before ischemia decreases postischemic hyperemia. Pentobarbital-anesthetized piglets underwent 15 min of complete global cerebral ischemia induced by elevation of intracranial pressure followed by 20 min of reperfusion. Before ischemia the animals were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 6, or 50 mg/kg, n = 6) or an equal volume of saline (10 ml, n = 8). Serial cerebral blood flow (radiolabeled microspheres) was measured at baseline and during ischemia and reperfusion. Forebrain postischemic hyperemia was documented after administration of saline (42 +/- 4 to 88 +/- 10 ml.min-1.100 g-1) and 10 mg/kg L-NAME (36 +/- 4 to 59 +/- 9 ml.min-1.100 g-1) but not after 50 mg/kg L-NAME (29 +/- 3 to 34 +/- 7 ml.min-1.100 g-1). However, the percent reduction in cerebral vascular resistance (CVR) fell during reperfusion to a similar extent in all three groups because of differences between groups in cerebral perfusion pressure changes during the protocol. CVR fell to the lowest level at 8 min of reperfusion in the saline-treated animals (2.0 +/- 0.16 to 0.68 +/- 0.05 mmHg.ml-1.min.100 g) compared with the L-NAME-treated animals (50 mg/kg: 4.0 +/- 0.3 to 1.8 +/- 0.2 mmHg.ml-1.min.100 g).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nitric oxide synthase inhibition on postischemic cerebral hyperemia. 754 58

We have investigated whether central inhibition of nitric oxide synthase (NOS) could modify the tissue damage of focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in rats. NG-Nitro-L-arginine methyl ester (L-NAME) was administered intracerebroventricularly at two doses 15 min prior to occlusion of the MCA, as well as 4 and 24 h following occlusion. After the injection of L-NAME, the catalytic activity of the constitutive NOS, considered to be mainly neuronal, was effectively suppressed in the subcortical gray matter bilaterally, but not in the ischemic territory. Seven days after the MCA occlusion, the brains were evaluated for histopathologic damage. High-dose administration of L-NAME (120 micrograms/kg 15 min prior to MCA occlusion, followed by 150 micrograms/kg 4 and 24 h after occlusion) produced an enlargement of the infarct area and increased the volume of ischemic damage. These results indicate that extensive inhibition of NOS by a central route can increase the cerebral infarct size in focal ischemia even if NOS is not inhibited in the ischemic tissue and suggest that NO may also play a potentially beneficial role as well as a neurodestructive role in the pathophysiological mechanisms of focal cerebral ischemia.
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PMID:Effects of central inhibition of nitric oxide synthase on focal cerebral ischemia in rats. 754 92

We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic metabolism of nitric oxide. We used magnetic resonance imaging (MRI) techniques to measure neuronal and cerebrovascular injury in a 2-h transient focal cerebral ischemia model in normoglycemic and hyperglycemic rats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Compared to normoglycemia, preexisting hyperglycemia increased the volume of brain tissue exhibiting hyperintensity in diffusion weighted MRI (DWI) by factors of 5.6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar increase in tissue volumes exhibiting hyperintense signal in T2-weighted MRI (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume MRI indicated a large focal no-reflow zone in hyperglycemic rats. Treatment with L-NAME eliminated the no-reflow zone in the hyperglycemic rats, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperintensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thus, nitric oxide is an important mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infarct volume.
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PMID:Nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester decreases ischemic damage in reversible focal cerebral ischemia in hyperglycemic rats. 755 44

It has been proposed that NO may function as an endogenous cardioprotectant. We have investigated whether modulation of NO levels (detected in coronary effluent by chemiluminescence) by a blocker of its synthesis, by supplementation of its precursor, and by administration of an NO donor can influence reperfusion arrhythmias in the isolated rat heart. Rat hearts were perfused with modified Krebs' solution and subjected to 5, 35, or 60 minutes of left regional ischemia followed by 10 minutes of reperfusion. NG-Nitro-L-arginine methyl ester (L-NAME), which blocks NO synthase, increased the incidence of reperfusion-induced ventricular fibrillation (VF) from 5% in the control condition to 35% after 60 minutes of ischemia (n = 20, P < .05). The profibrillatory effect of L-NAME was prevented in hearts coperfused with 1 or 10 mmol/L L-arginine (an NO precursor) but persisted in hearts coperfused with D-arginine (1 mmol/L). L-NAME did not increase VF susceptibility in hearts reperfused after 5 or 35 minutes of ischemia. L-NAME caused sinus bradycardia (264 +/- 10 versus 309 +/- 5 bpm in control groups, P < .05) and reduced coronary flow before ischemia (6.2 +/- 0.6 versus 9.2 +/- 0.6 mL.min-1.g-1 tissue in controls, P < .05). L-NAME reduced coronary effluent NO levels after 60 minutes of ischemia; during the first minute of reperfusion, values were reduced from 1457 +/- 422 to 812 +/- 228 pmol.min-1.g-1 (P < .05). This effect was prevented by coperfusion with L-arginine (10,344 +/- 1730 pmol.min-1.g-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of NO modulation on cardiac arrhythmias in the rat isolated heart. 755 53

This study was designed to examine if acute systemic blockade of nitric oxide (NO) production by inhibition of nitric oxide synthase (NOS) with N-omega-nitro-L-arginine methyl ester (L-NAME) would worsen the severity of ischemic acute renal failure (ARF). Initially three groups of rats, were studied: 45 min of bilateral renal ischemia (I) alone, Group I; L-NAME (L; 10 mg/kg BW, i.v.) alone, Group L; and L-NAME administered 15 min before renal ischemia, Group L+I. We observed, however, a 60% mortality in Group I+L during the first 4 h of reflow. Captopril, administered acutely 15 min before L-NAME in an attempt to offset any detrimental effects of increased angiotensin II generation in response to renal ischemia, failed to obviate the mortality because 67% of rats in this group (Group C+L+I) also died. Therefore, additional studies were performed in rats instrumented for cardiovascular studies to evaluate the acute hemodynamic responses during the first 90 min of reperfusion following renal ischemia in rats pretreated with L-NAME. As expected, L-NAME injection was accompanied by a 25-30 mm Hg increase in mean systemic arterial pressure (SAP) (p < 0.05), a bradycardia (p < 0.02), and a decrease in cardiac output (CO) (p < 0.02). The increase in SAP was due exclusively to an increase in systemic vascular resistance (SVR) (p < 0.01). Ischemia and reflow in the L-NAME-treated rats were attended by a progressive increase in SVR and a progressive decrease in CO such that by the end of 45 min of reperfusion SVR had increased 10-fold and CO had decreased to one third of its initial rate (both p < 0.02). Pulmonary artery pressure (PAP) increased promptly following L-NAME injection. Total pulmonary resistance (PRT) increased significantly by the end of reperfusion. L-NAME in combination with renal ischemia and reflow induces a large increase in both SVR and PRT, and is accompanied by a 70% reduction in CO and substantial mortality.
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PMID:Nitric oxide synthase inhibition and acute renal ischemia: effect on systemic hemodynamics and mortality. 756 11

Ischemic preconditioning (PC) has been shown to limit ischemia- and reperfusion-induced arrhythmias. We wished to determine whether the antiarrhythmic effect of PC would be affected by inhibition of the L-arginine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reperfusion were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of PC (three cycles of 2-min coronary artery occlusion and 5-min reperfusion) on development of reperfusion-induced arrhythmias after 5-min coronary artery occlusion was studied in 12 rats. In 24 other rats, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i.v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 100 mg/kg i.v., n = 12) was administered to rats 5 min before coronary artery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent group to 17%, decreased the incidence of ventricular tachycardia (VT) from 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solvent group, respectively). L-NAME and L-NMMA did not significantly affect the protective effect of PC on reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway? 759 18


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